Metabolism of methacrylonitrile to cyanide: in vitro studies.
In liver fractions from male Sprague-Dawley rats, the metabolism of methacrylonitrile (MeAN) to cyanide (CN-) was localized in microsomal fraction and required reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen for maximal activity. The biotransformation of MeAN to CN- was characterized with respect to time, microsomal protein concentration, pH, and temperature. Metabolism of MeAN was increased in microsomes obtained from phenobarbital-treated rats (310% of control) and decreased with CoCl2 and SKF 525 A treatments (55% and 61%, respectively). Addition of the epoxide hydratase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN- from MeAN. Addition of glutathione, cysteine, D-penicillamine, and 2-mercaptoethanol enhanced the released of CN- from MeAN. These findings indicate that MeAN is metabolized to CN- via a cytochrome P-450-dependent mixed-function oxidase system.
Farooqui
M Y
MY
Department of Biological Sciences, University of Texas Pan American, Edinburg 78539.
Diaz
R G
RG
Cavazos
R
R
D000818:Animals; D001711:Biotransformation; D003486:Cyanides / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism*; D010101:Oxygen Consumption; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism
D003486:Cyanides; D008689:Methacrylates; D009570:Nitriles; C008385:methacrylonitrile; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D005978:Glutathione; D010634:Phenobarbital